T cells are a class of lymphocytes which mediate cellular immune responses in higher animals. When an organism is exposed to a foreign substance that can alter the surface of host cells, T cells that recognize the foreign antigen are activated, resulting in T-cell binding to and destruction of the altered cells.
The ontogeny of T cells, and the expression of different cellular antigens during T cell differentiation has been studied. T cells originate from precursor cells made in the bone marrow, and these cells further differentiate into virgin T cells in the thymus. A portion of the cells migrate from the thymus to T-cell domains of peripheral lymphoid organs. Probably as a result of antigen stimulation, some of the T cells are converted to long-lived mature T cells. The mature cells possess surface receptors for foreign antigens, and upon stimulation, proliferate to form functional T cells.
Monoclonal antibodies against T cells have been used to identify a number of surface molecules which are expressed during intrathymic ontogeny (Reinherz, 1983). This has allowed the definition of at least three discrete stages of T-cell differentiation (Reinherz, 1980). The earliest identified T-lineage cells express the sheep erythrocyte receptor, T11(stage I). Later, thymocytes express T6, T4 and T8 antigens (stage II). With further maturation, the expression of the surface antigen T6 is shut off, thymocytes acquire the T3/T-cell receptor structure and ultimately appear in the periphery as either T4.sup.+ T8.sup.- or T4.sup.- T8.sup.+ cells (stage III).
Although monoclonal antibodies have helped define surface structures on T cells (Haynes), most T-cell surface molecules have remained elusive to serologic detection. There are as many as 200 different mRNA sequences expressed in T cells that are absent in B cells. A third of those sequences are membrane-associated molecules (Hedrick). Identification of membrane-associated molecules, and elucidation of their function and mechanism of action, is difficult because of the technical problems associated with the isolation and purification of proteins which have hydrophobic regions which can cause protein aggregation. In addition, there are limitations in the source of the product.
The problem of identifying surface antigens, and studying their role in cellular development and function, can also be approached with recombinant DNA methods. Potentially, these methods allow for the cloning and sequencing of coding sequences which are expressed specifically at certain developmental stages in T cells, and identification and expression of proteins and/or peptide regions associated with these coding sequences.